NCT07241234 · Agios Pharmaceuticals, Inc.
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
What this study is about
The primary purpose of this study is to assess the safety and how well patients handle the treatment of AG-181 in subjects with Phenylketonuria (PKU).
View original scientific description
The primary purpose of this study is to assess the safety and tolerability of AG-181 in subjects with Phenylketonuria (PKU).
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Diagnosis of PKU, defined as documented presence of 2 mutant alleles in the phenylalanine hydroxylase (PAH) gene, of which at least 1 is the R408W mutation, as determined during Screening per the genotyping performed by the study central genotyping laboratory.
- At least 1 plasma Phe concentration greater than (\>) 600 micromoles per liter (μmol/L) in the 52 weeks before providing informed consent.
- Average concentration of plasma Phe \> 600 μmol/L in Phe samples taken during Screening, with no individual assessment below 360 μmol/L. Any Phe samples taken after Day -20 will not be included.
- Body mass index (BMI) greater than or equal to (≥) 18.0 kilograms per meter square (kg/m\^2) to lesser than or equal to (≤) 35.0 kg/m\^2 and weight ≥ 50 kilograms (kg) at any time during the Screening Period.
- Documented approval from a dietitian confirming that the subject can maintain their diet consistent in protein and Phe intake throughout the study as outlined in the Diet Manual. Key
Exclusion criteria
- Prior exposure to AG-181.
- Receiving inhibitors of P-glycoprotein (P-gp) that have not been stopped for ≥ 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) before administration of the first dose of study drug.
- Receiving products that are strong inhibitors or strong inducers of cytochrome P450 CYP1A2, CYP2C8, or CYP3A that have not been stopped for ≥ 28 days before administration of the first dose of study drug.
- Receiving treatment with an acid-reducing agent, including but not limited to proton pump inhibitors and H2 blockers. Short-acting acid-reducing agents such as calcium carbonate are permitted.
- Any preexisting condition that could (in the opinion of the Investigator) interfere with gastrointestinal anatomy or motility that may disrupt the absorption, metabolism, and/or excretion of the study drug.
- Any preexisting condition that could (in the opinion of the Investigator) interfere with hepatic or renal function that may disrupt the absorption, metabolism, and/or excretion of the study drug.
- Inability to tolerate oral medication.
- Unwillingness to washout from tetrahydrobiopterin (BH4) supplementation (eg, sapropterin dihydrochloride, Kuvan), pegvaliase-pqpz (Palynziq), or any other PKU therapy by Day -30 during Screening.
Where
- Indianapolis, Indiana
- Pittsburgh, Pennsylvania
- Dallas, Texas
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 23, 2026 · Source of record for eligibility and locations